| First Author | Shin GC | Year | 2014 |
| Journal | Biochim Biophys Acta | Volume | 1842 |
| Issue | 9 | Pages | 1648-57 |
| PubMed ID | 24769044 | Mgi Jnum | J:217039 |
| Mgi Id | MGI:5612945 | Doi | 10.1016/j.bbadis.2014.04.016 |
| Citation | Shin GC, et al. (2014) Hepatocystin contributes to interferon-mediated antiviral response to hepatitis B virus by regulating hepatocyte nuclear factor 4alpha. Biochim Biophys Acta 1842(9):1648-57 |
| abstractText | Hepatocystin/80K-H is known as a causative gene for autosomal dominant polycystic liver disease. However, the role of hepatocystin in hepatitis B virus-related liver disease remains unknown. Here, we investigated the role of hepatocystin on the cytokine-mediated antiviral response against hepatitis B virus infection. We investigated the antiviral effect and mechanism of hepatocystin by ectopic expression and RNAi knockdown in cell culture and mouse livers. Hepatocystin suppressed the replication of hepatitis B virus both in vitro and in vivo. This inhibitory effect was HBx-independent and mediated by the transcriptional regulation of viral genome via the activation of exogenous signal-regulated kinase 1/2 and the reduced expression of hepatocyte nuclear factor 4alpha, a transcription factor essential for hepatitis B virus replication. The amino-terminal region of hepatocystin was essential for regulation of this antiviral signaling pathway. We also found that hepatocystin acts as a critical component in interferon-mediated mitogen-activated protein kinase signaling pathway, and the interferon-induced antiviral activity against hepatitis B virus is associated with the expression levels of hepatocystin. We demonstrated that hepatocystin plays a critical role in modulating the susceptibility of hepatitis B virus to interferon, suggesting that the modulation of hepatocystin expression is important for cytokine-mediated viral clearance during hepatitis B virus infection. |
